Adverse birth outcome and associated factors among mothers with HIV who gave birth in northwest Amhara region referral hospitals, northwest Ethiopia, 2020

Adverse birth outcomes are a common cause of health problems in developing nations and have a significant negative impact on infant health as well as financial costs to families, communities, and the world. Mothers with HIV may be at increased risk of adverse birth outcomes. However, there is a limited study about adverse birth outcomes among mothers with HIV around the world including in Ethiopia. Therefore this study aimed to assess adverse birth outcomes and associated factors among mothers with HIV Facility based cross-sectional study was conducted among mothers with HIV who gave birth in northwest Amhara region referral hospitals from September 2016 to September 2019. Simple random sampling was used to select 590 mothers. Bivariable and multivariable logistic regressions were carried out to identify factors. Statistical significance was declared by using a p-value < 0.05. An adjusted odds ratio was used to show the magnitude of the association. Out of a total of 590 mothers, the prevalence of adverse birth outcomes among HIV-positive mothers was 21% (95% CI 17.8–24.6%). History of spontaneous abortion [AOR = 1.9, 95% CI (1.19, 3.70)], PROM [AOR = 3.55, 95% CI (1.72, 7.30)], opportunistic infection [AOR = 3.38, 95% CI (1.50, 8.22)], pre-pregnancy BMI of < 18.5 [AOR = 5.61, 95% CI (1.97, 15.91)], MUAC < 23 cm [AOR = 2.56, 95% CI (1.10, 5.97)], and ANC visit of < 4 times [AOR = 3.85, 95% CI (2.34, 6.55)] were significantly associated with Adverse birth outcome. The prevalence of adverse birth outcomes was high. Abortion history, MUAC, BMI, Opportunistic infection, PROM, and a number of ANC visits were associated with adverse birth outcomes. This study suggests to increase number of antenatal care follow-ups, prevent and treat opportunistic infections, and focus on early detection and treatment of pregnancy-related complication


Methodology
Study design and period. An institutional-based cross-sectional study was conducted among mothers delivered from September 2016 to September 2019 in northwest Amhara region referral hospitals and the data was extracted from March 3 to May 18/2020. Study area. Amhara national region is one of the ten national states in Ethiopia which is found in the Northern part of Ethiopia. The region has 80 hospitals, 847 health centers, and 3342 health posts. there are 6 referral hospitals-namely Gondar University Comprehensive Specialized Hospital (GUCSH), Felegehiwot Comprehensive Specialized Hospital (FCSH), Dessie Referral Hospital (DRH), Debre-Markos Referral Hospital (DMRH), Debre-Birhan Referral Hospital (DBRH) and Debre tabor referral hospitals. Three out of six referral hospitals were found in the Northwest part of the Amhara region. These include: -the University of Gondar comprehensive and specialized Hospital (UoGCSH), Felege Hiwot comprehensive, and specialized hospital (FHCS), and Debre Markos referral hospital. Each referral hospital's catchment population is estimated to be 5-7 million people. The annual average number of births in each hospital is 6000 per year. according to the hospital report. All three hospitals are providing full ANC/PMTCT, ART, delivery services, and ultrasound-guided obstetric care. www.nature.com/scientificreports/ Eligibility criteria. All mothers with HIV delivered from September 2016-September 2019 in northwest Amhara region referral hospitals with a gestational age of 28 weeks and above were included in the study. However, mothers who had unknown or unreliable last normal menstrual period (LNMP) with the absence of ultrasound evidence and a mother with unrecorded birth outcome were excluded from the study.
Variables of the study. The  Operational definition. Adverse birth outcomes: A woman who had at least one of the following stillbirth, low birth weight, preterm birth 22 . Preterm birth: Preterm is defined as babies born alive before 37 weeks of gestation but after viability (28 weeks of gestation) and gestational age was calculated based on LNMP or first-trimester ultrasound result 23 .
Low birth weight: a birth weight < 2500 g irrespective of gestational age 24 . Stillbirth: dead birth after the 28th week of gestation and before the expulsion from the uterus 25 . APH: defined as any vaginal bleeding in the mother after 28 weeks of gestation as documented in the records by the attending clinician 26 .
PIH: defined clinically as a blood pressure of > 140/90 mmHg after 20 weeks of gestation with or without proteinuria and/or edema as diagnosed and documented by the attending clinician 26  Sample size determination and sampling procedure. The required sample size was determined by using the single population proportion formula n = za 2 /2p(1 − p)/d 2 by considering the prevalence PTB among mothers with HIV was 16.6% 16 , 95% confidence interval (CI), 3% margin of error to yield a total of 590 study participants. The total sample size was proportionally allocated for the three Hospitals depending on their load of delivery. A simple random sampling technique was employed to select the study participant's medical records. The delivery registration logbooks were used as a sampling frame and selected each record for our study used a computer-generated random number. Whenever the selected chart did not fulfill the inclusion criteria, the next medical record was considered ( Fig. 1.).
Data collection tool. The patient's medical records were used as a source of data. The data, consisting of socio-demographic variables, clinical and obstetric history as well as birth outcome, were collected using a data extraction tool. Maternal BMI was determined by using the mother's pre-pregnancy, initial weight, and height from their ART and PMTCT follow-up. Newborn weight was measured using standard beam balance within the first hour of birth Six Bachelor of science (BSc) Midwives collected the data, while 3 midwives who have a second degree in clinical midwifery supervised the data collection process. Data quality was maintained by the following data quality control mechanisms; A 5% preliminary chart review was conducted in the Gondar university comprehensive and specialized hospital before the actual data collection and amendments were considered based on the result of a preliminary chart review. One day of training was given to data collectors and supervisors. Strict supervision of the data collection was carried out throughout the data collection period. The collected data was checked for its consistency and completeness before any attempt to enter, code, and analyze it.
Data processing and analysis. Data were coded and then entered using EPI data version 4.6 and exported to SPSS. The final statistical analysis was done by SPSS version 25. Before analysis, data were cleaned using frequency; listing, and sorting to identify any missed values, and then corrections were made by revising the original questionnaire. There are different techniques of missing data management. Deletion, replacement using the mean or mode of the data (mean substitution/replacement) or predicted values from a regression to substitute the missing values. So for this study, we had used replacement by mean for continuous and Mode for categorical variable if less than 20% of values are missed in one variable, but if more than 20% of values are missed in one variable, we discard the variables. Descriptive statistics were made for categorical variables using frequencies.
The result was presented using texts and tables. a multivariable binary logistic regression model was used to assess the association between dependent and independent variables. P-value < 0.05 and Adjusted Odds Ratio (AOR) with 95% CI was used to declare statistically significant predictors in multivariable analysis.

Discussion
The finding of the study showed that the prevalence of adverse birth outcomes was 126 (21.4% 95% CI 18-25%) among which 10 (1.7%) were stillbirth, 74 (12.5%) were preterm and 98(16.6%) were low birth weight. These figures were comparable with findings from studies conducted in Hosanna (24.5%) 13 , Hawassa (18.3%), Tanzania (18%), and Ghana (19%) of mothers who experienced adverse birth outcomes 27,28 . The overall prevalence of adverse birth outcomes in this study was slightly lower than in studies conducted in Ethiopia, Dessie, 32.5% 24 The discrepancy might be due to a difference in the study area and study participant's residents and age group. the study conducted in Dessie used 30-40% of rural resident participants and rural resident mothers are highly prone to adverse birth outcome than those living in urban 29 and 15% of study participants in Dessie was Age group < 20 years and this age group is highly prone adverse birth outcome 13,30 .
The overall prevalence of adverse birth outcomes in this study is slightly higher than in a study done in Kembata (13.9%) 25 this might be due to the difference in the study area, this study is done in referral hospitals whereas a study done in Kembata were in a health center and primary hospital. This may be because most normal deliveries take place in health centers while more complicated ones are referred to the tertiary hospital contributing to higher rates of adverse birth outcomes at referral hospitals 20 and study participants in this study were HIV positive and HIV increases the risk of having adverse birth outcome 23,31 or it might be due to compromised immune system of HIV positive mothers increase the risk of opportunistic infection, which contributes to the occurrence of adverse birth outcome.
Mothers who had opportunistic infections during pregnancy were found to be more than 3 times more likely to have Adverse birth outcomes than mothers who did not have Opportunistic infections. this finding is consistent with studies done in Nigeria 32 . This might be due to opportunistic infections compromising the nutritional status of the mother and fetal growth, for instance, infants from mothers with syphilis are often premature 33 .
In HIV-positive women the risk of having adverse birth outcomes were more than fourfold higher in a mother who had pre-pregnancy BMI less than 18.5 when compared with mothers having pre-pregnancy BMI ≥ 18.5. This result was similar to a study done in northwest Ethiopia public hospitals 16 . Moreover, In these findings mothers with MUAC, less than 23 cm were also found to experience adverse birth outcomes when compared with those with MUAC greater than 23 cm this result is in agreement with the study done in Dessie referral hospital 20 This might be due to intergenerational effect of malnutrition that leads to LBW 29 or poor nutritional status of the mother compromised the immune system and increase the risk of opportunistic infections that leads to preterm birth.
In this study, mothers with less than four times ANC visits were 3.5 times at high risk to have Adverse birth outcomes than those with four and more visits. This result was similar with study done in Mekell Hospital 30 Debre Table 2. pregnancy and labor-related complications of mothers with HIV delivered in west Amhara regional state referral hospitals (N = 590). Pregnancy-related complication during the current pregnancy was significantly associated with Adverse birth outcome, according to the finding of this research the risk of having adverse birth outcome among mothers who had PROM during the current pregnancy were more than 3 times higher than those mothers who had no PROM. This finding is consistent with a study done Debre tabor 23 , East Africa 37 , Ghana and Kenyatta national hospital 38,39 , Axum and Adwa public hospitals 40 , and Hosanna 13 . This might be due to that labor will spontaneously initiate within a week after preterm PROM 23 , or this might be due to -provider-initiated early termination of pregnancy to manage pregnancy-related complications 20 .

Limitation of study
Since this study is hospital-based, it doesn't include mothers who gave birth at home, which makes it difficult to conclude the general population. In addition, the data used were secondary there may be bias and incomplete information or missing variables.